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Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes

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chinese Journal of Integrative medicine 2024年第3期30卷 222-229页

作者： ZHANG Shuo LI Hong-jin YANG Chun-mei LIU Liu SUN Xiao-ying WANG Jiao CHEN Si-ting LU Yi HU Man-qi YAN Ge ZHOU Ya-qiong MIAO Xiao LI Xin LI Bin Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai200437China institute of Dermatology Shanghai Academy of Traditional Chinese MedicineShanghai201203China Department of integrated Traditional chinese and western medicine Shanghai Skin Disease HospitalTongji University School of MedicineShanghai200443China

Objective:To determine the role of Tripterygium wilfordii multiglycoside(TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.Methods:Mouse models of psoriatic dermatitis were established by imiquimod(IMQ).Twelve male BALB/c mice were assigned to MQ or IMQ+TGW groups according to a random number table.Histopathological changes in vivo were assessed by hematoxylin and eosin staining.Ratios of immune cells and cytokines in mice,as well as PAM212 cell proliferation in vitro were assessed by flow cytometry.Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.Results:TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45^(+)cells,neutrophils and T lymphocytes(all P<0.01).Moreover,TGW significantly attenuated keratinocytes(KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin(IL)-17A,IL-23,tumor necrosis factor α,and chemokine(C-X-C motif) ligand 1(P<0.01 or P<0.05).Furthermore,it reduced the number of γδ T17 cells in skin lesion of mice and draining lymph nodes(P<0.01).Conclusions:TGW improved psoriasis-like inflammation by inhibiting KCs proliferation,as well as the associated immune cells and cytokine expression.It inhibited IL-17 secretion from γδ T cells,which improved the immune-inflammatory microenvironment of psoriasis.

关键词： psoriasis Tripterygium wilfordii multiglycoside γδT cells inflammation chinese medicine

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Huangqin Decoction Delays Progress of Colitis-Associated Carcinogenesis by Regulating Nrf2/HO-1 Antioxidant Signal Pathwayin Mice

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chinese Journal of Integrative medicine 2024年第2期30卷 135-142页

作者： GU Li-mei LI He-zhong GAO Lei LI Hui WEI Lan-fu PAN Cheng-yu WU Ke-xuan TIAN Yao-zhou Department of Gastrointestinal Endoscopy Affiliated Hospital of Nanjing University of Chinese MedicineNanjing(210029)China Department of Gastroenterology Affiliated Hospital of Integrated Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing(210028)China School of integrated chinese and western medicine Nanjing University of Chinese MedicineNanjing(210023)China

Objective:To investigate the effect of Huangqin Decoction(HQD)on nuclear factor erythroid 2 related-factor 2(Nrf2)/heme oxygenase(HO-1)signaling pathway by inducing the colitis-associated carcinogenesis(CAC)model mice with azoxymethane(AOM)/dextran sodium sulfate(DSS).Methods:The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-Q-TOF-MS/MS)to determine the molecular constituents of HQD.Totally 48 C57BL/6J mice were randomly divided into 6 groups by a random number table,including control,model(AOM/DSS),mesalazine(MS),low-,medium-,and high-dose HQD(HQD-L,HQD-M,and HQD-H)groups,8 mice in each group.Except for the control group,the mice in the other groups were intraperitoneally injected with AOM(10 mg/kg)and administrated with 2.5%DSS orally for 1 week every two weeks(totally 3 rounds of DSS)to construct a colitis-associated carcinogenesis mouse model.The mice in the HQD-L,HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925,5.85,and 11.7 g/kg,respectively;the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg(totally 11 weeks).The serum levels of malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by enzyme-linked immunosorbent assay.The mRNA and protein expression levels of Nrf2,HO-1,and inhibitory KELCH like ECH-related protein 1(Keap1)in colon tissue were detected by quantitative real-time PCR,immunohistochemistry,and Westem blot,respectively.Results:LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin,paeoniflorin,and glycyrrhizic acid.Compared to the control group,significantly higher MDA levels and lower SOD levels were observed in the model group(P<0.05),whereas the expressions of Nrf2 and HO-1 were significantly decreased,and the expression of Keap1 increased(P<0.01).Compared with the model group,serum MDA level was decreased and SOD level was increased in the HQD-M,HQD-H and MS groups(P<0.05).Higher expressions of Nrf2 and HO-1 were observed in the HQD groups.Co

关键词： Huangqin Decoction colitis-associated carcinogenesis nuclear factor erythroid 2 related-factor 2/heme oxygenase signaling pathway oxidative stress chinese medicine

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Artificial intelligence for the detection of glaucoma with SD-OCT images:a systematic review and Meta-analysis

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 408-419页

作者： Nan-Nan Shi Jing Li Guang-Hui Liu Ming-Fang Cao Department of Ophthalmology Affiliated People’s Hospital(Fujian Provincial People’s Hospital)Fujian University of Traditional Chinese MedicineFuzhou 350004Fujian ProvinceChina eye institute of integrated chinese and western medicine Fujian University of Traditional Chinese MedicineFuzhou 350004Fujian ProvinceChina

●AIM:To quantify the performance of artificial intelligence(AI)in detecting glaucoma with spectral-domain optical coherence tomography(SD-OCT)images.●METHODS:Electronic databases including PubMed,Embase,Scopus,ScienceDirect,ProQuest and Cochrane Library were searched before May 31,2023 which adopted AI for glaucoma detection with SD-OCT images.All pieces of the literature were screened and extracted by two investigators.Meta-analysis,Meta-regression,subgroup,and publication of bias were conducted by Stata16.0.The risk of bias assessment was performed in Revman5.4 using the QUADAS-2 tool.●RESULTS:Twenty studies and 51 models were selected for systematic review and Meta-analysis.The pooled sensitivity and specificity were 0.91(95%CI:0.86–0.94,I2=94.67%),0.90(95%CI:0.87–0.92,I2=89.24%).The pooled positive likelihood ratio(PLR)and negative likelihood ratio(NLR)were 8.79(95%CI:6.93–11.15,I2=89.31%)and 0.11(95%CI:0.07–0.16,I2=95.25%).The pooled diagnostic odds ratio(DOR)and area under curve(AUC)were 83.58(95%CI:47.15–148.15,I2=100%)and 0.95(95%CI:0.93–0.97).There was no threshold effect(Spearman correlation coefficient=0.22,P>0.05).●CONCLUSION:There is a high accuracy for the detection of glaucoma with AI with SD-OCT images.The application of AI-based algorithms allows together with“doctor+artificial intelligence”to improve the diagnosis of glaucoma.

关键词： artificial intelligence spectral-domain optical coherence tomography glaucoma Meta-analysis

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Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori

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World Journal of Gastroenterology 2024年第24期30卷 3086-3105页

作者： Miao-Miao Lin Shan-Shan Yang Qiu-Yue Huang Guang-Hui Cui Xiao-Fen Jia Yao Yang Zong-Ming Shi Hui Ye Xue-Zhi Zhang Department of integrated Traditional chinese and western medicine Peking University First HospitalBeijing 100034China institute of integrated Traditional chinese and western medicine Peking UniversityBeijing 100034China

BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to eradication.It has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in vitro.METHODS In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients.In vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,respectively.The most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation.This assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation.Crystalline violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains.The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction.Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups.RESULTS HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the strain.QHD had strong bacteriostatic and bactericidal effects on H

关键词： Qingre Huashi decoction Helicobacter pylori Drug resistance Biofilm Metabolomics

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Emodin suppresses alkali burn-induced corneal inflammation and neovascularization by the vascular endothelial growth factor receptor 2 signaling pathway

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Journal of Traditional chinese medicine 2024年第2期44卷 268-276页

作者： ZHENG Xueying GUO Liang LAI Siyi LI Fengyue LIANG Mingli LIU Wanting MENG Chun LIU Guanghui Department of Bioengineering College of Biological Science and BiotechnologyFuzhou UniversityFuzhou 350104China eye institute of integrated chinese and western medicine Fujian University of Traditional Chinese MedicineFuzhou 350004China Department of Ophthalmology Affiliated People's Hospital(Fujian Provincial People's Hospital)Fujian University of Traditional Chinese MedicineFuzhou 350004China

OBJECTIVE:To investigate the effects of emodin on alkali burn-induced corneal inflammation and neovascularization.METHODS:The ability of emodin to target vascular endothelial growth factor receptor 2(VEGFR2)was predicted by molecular docking.The effects of emodin on the invasion,migration,and proliferation of human umbilical vein endothelial cells(HUVEC)were determined by cell counting kit-8,Transwell,and tube formation assays.Analysis of apoptosis was performed by flow cytometry.CD31 levels were examined by immunofluorescence.The abundance and phosphorylation state of VEGFR2,protein kinase B(Akt),signal transducer and activator of transcription 3(STAT3),and P38 were examined by immunoblot analysis.Corneal alkali burn was performed on 40 mice.Animals were divided randomly into two groups,and the alkali-burned eyes were then treated with drops of either 10μM emodin or phosphate buffered saline(PBS)four times a day.Slitlamp microscopy was used to evaluate inflammation and corneal neovascularization(CNV)in all eyes on Days 0,7,10,and 14.The mice were killed humanely 14 d after the alkali burn,and their corneas were removed and preserved at-80℃ until histological study or protein extraction.RESULTS:Molecular docking confirmed that emodin was able to target VEGFR2.The findings revealed that emodin decreased the invasion,migration,angiogenesis,and proliferation of HUVEC in a dose-dependent manner.In mice,emodin suppressed corneal inflammatory cell infiltration and inhibited the development of corneal neovascularization induced by alkali burn.Compared to those of the PBS-treated group,lower VEGFR2 expression and CD31 levels were found in the emodintreated group.Emodin dramatically decreased the expression of VEGFR2,p-VEGFR2,p-Akt,p-STAT3,and p-P38 in VEGF-treated HUVEC.CONCLUSION:This study provides a new avenue for evaluating the molecular mechanisms underlying corneal inflammation and neovascularization.Emodin might be a promising new therapeutic option for corneal alkali burns.

关键词： alkali burn emodin corneal inflammation corneal neovascularisation vascular endothelial growth factor receptor-2 signal transduction

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Effects of NLRP3 Inflammasome Mediated Pyroptosis on Cardiovascular Diseases and Intervention Mechanism of chinese medicine

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chinese Journal of Integrative medicine 2024年第5期30卷 468-479页

作者： ZHONG Yi LI Xin-yue LIANG Tian-jun DING Bao-zhu MA Ke-xin REN Wen-xuan LIANG Wen-jie College of integrated Traditional chinese and western medicine Hebei University of Chinese MedicineHebei Key Laboratory of Integrated Traditional Chinese and Western Medicine in Liver and Kidney DiseasesInstitute of Integrated Traditional Chinese and Western MedicineShijiazhuang 050200China Department of Cardiovascular Internal medicine the Second Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi Province 332000China Graduate School Hebei Medical UniversityShijiazhuang 050017China Rural Physician College Hebei Medical UniversityShijazhuang 050017China Medical Department the First Hospital of Hebei Medical UniversityShijiazhuang 050030China

Activation of the NOD-like receptor protein 3(NLRP3)inflammasome signaling pathway is an important mechanism underlying myocardial pyroptosis and plays an important role in inflammatory damage to myocardial tissue in patients with cardiovascular diseases(CVDs),such as diabetic cardiomyopathy,ischemia/reperfusion injury,myocardial infarction,heart failure and hypertension.Noncoding RNAs(nc RNAs)are important regulatory factors.Many chinese medicine(CM)compounds,including their effective components,can regulate pyroptosis and exert myocardium-protecting effects.The mechanisms underlying this protection include inhibition of inflammasome protein expression,Toll-like receptor 4–NF-κB signal pathway activation,oxidative stress,endoplasmic reticulum stress(ERS),and mixed lineage kinase 3 expression and the regulation of silent information regulator 1.The NLRP3 protein is an important regulatory target for CVD prevention and treatment with CM.Exploring the effects of the interventions mediated by CM and the related mechanisms provides new ideas and perspectives for CVD prevention and treatment.

关键词： pyroptosis cardiovascular diseases chinese medicine NOD-like receptor protein 3 mechanisms

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Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension:A randomized,double-blind,placebo-controlled trial

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Journal of Integrative medicine 2024年第4期22卷 484-492页

作者： Jun Xie Yu-long Ma Ming-tai Guia Lei Yao Jian-hua Li Ming-zhu Wang Xun-jie Zhou Yi-fan Wang Ming-yi Zhao Hui Cao Bo Lu De-yu Fu Department of Cardiology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese Medicine Shanghai University of Traditional chinese medicine

Background:Hypertension,a prevalent disease,is a significant risk factor for coronary heart disease.Huoxue Qianyang Qutan Recipe (HQQR),a traditional chinese herbal remedy,has been used for treating hypertension over several years.Objective:This study assesses HQQR’s efficacy for controlling blood pressure among patients with hypertension related to blood stasis,yang hyperactivity and phlegm.Design,setting,participants and interventions:A randomized controlled trial was conducted at the Yueyang Hospital of integrated Traditional chinese and western medicine,Shanghai University of Traditional chinese medicine,China,from July 2020 to June 2022.Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography.Participants aged18–80 years,exhibiting traditional chinese medicine syndromes of blood stasis,yang hyperactivity or phlegm,along with grades 1 or 2 hypertension,were randomly categorized into two groups.The intervention group was given HQQR granules alongside conventional hypertension treatment,while the control group was given placebo granules in addition to conventional treatment for 12 weeks.Main outcome measures:The primary outcome was clinic blood pressure,whereas secondary outcomes included metabolic indices (e.g.,homeostasis model assessment of insulin resistance[HOMA-IR],total cholesterol[TC],low-density lipoprotein cholesterol and triglyceride),target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio[UACR]) and inflammation indices(interleukin-6[IL-6]and high-sensitivity C-reactive protein[hs-CRP]).Results:HQQR’s primary components were identified as salvianolic acid B,emodin and ferulic acid.Of the216 participants (108 in each group),compared to the control,the intervention group exhibited significant improvements (P<0.001) in clinic systolic blood pressure ([136.24±7.63]vs[130.06±8.50]mmHg),clinic diastolic blood pressure ([84.34±8.72]vs[80.46±6.05]mmHg),home systolic blood pressure([131.64±8.74]vs[122.36±8.45]mmH

关键词： chinese herbal compound Glycolipid metabolism Huoxue Qianyang Qutan Recipe Hypertension Inflammatory Target organ damage

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Chang’an decoction(肠安方) alleviates endoplasmic reticulum stress by regulating mitofusin 2 to improve colitis

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Journal of Traditional chinese medicine 2024年第3期44卷 427-436页

作者： CHEN Youlan DING Mingming HUANG Chaoyuan ZHENG Yiyuan LIU Fengbin institute of integrated Traditional chinese and western medicine Digestive Diseases Shuguang HospitalShanghai University of Traditional Chinese Medicine Department of Oncology Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai the First Clinical Medical School Guangzhou University of Chinese Medicine Department of Gastroenterology the First Affiliated Hospital of Guangzhou University of Chinese Medicine Baiyun Hospital of the First Affiliated Hospital of Guangzhou University of chinese medicine

OBJECTIVE: To evaluate the protective effects of Chang'an decoction(肠安方, CAD) on colitis, and investigate the potential mechanisms underlying these effects from the perspectives of endoplasmic reticulum(ER) stress induced by mitofusin 2(MFN2). METHODS: The composition of CAD was identified by liquid chromatography-mass spectrometry technology. A mice model of dextran sulfate sodium(DSS) induced colitis was established and therapeutic effects of CAD were determined by detecting body weight, disease activity index, colon length and histopathological changes. Then, the expression levels of MFN2, ER stress markers and Nucleotide-binding domain and leucine-rich repeat protein3(NLRP3) relevant proteins were detected by polymerase chain reaction(PCR), western blot, immunohistochemistry and immunofluorescence staining. Subsequently, knockdown and overexpression cell model were constructed to further investigate the underlying mechanism of MFN2 mediating ER stress and energy metabolism by PCR, western blot, electron microscopy and reactive oxygen species(ROS) staining. Finally, inflammatory indicator and tight junction proteins were measured by PCR and immunofluorescence staining to evaluate the protective effects of CAD. RESULTS: Results showed that the indispensable regulatory role of MFN2 in mediating ER stress and mitochondrial damage was involved in the protective effects of CAD on colitis in mice fed with DSS. Network pharmacology analysis also revealed CAD may play a protective effect on colitis by affecting mitochondrial function. In addition, our data also suggested a causative role for MFN2 in the development of inflammatory responses and energy metabolic alterations by constructing a knockdown and overexpression cell model whereby alter proper ER-mitochondria interaction in Caco-2 cells. Furthermore, relative expression analyses of ER stress markers and NLRP3 inflammasome showed the onset of ER stress and activation of NLRP3 inflammasome, which is consistent with the above findings. In contrast, intervention of

关键词： Chang'an decoction colitis endoplasmic reticulum stress mitochondrial damage mitofusin 2

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Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1500-1513页

作者： Jian-Rong Sun Dong-Mei Chen Rong Huang Rui-Tao Wang Li-Qun Jia School of Clinical medicine Beijing University of Chinese MedicineBeijing 100029China integrated chinese and western medicine Oncology China-Japan Friendship HospitalBeijing 100029China

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those i

关键词： Esophageal squamous cell carcinoma Intraepithelial neoplasia Tumorigenesis Transcriptome sequencing Biomarkers Immune cell infiltration 4-nitroquinoline 1-oxid

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Therapeutic effect of Wendan Decoction combined with mosapride on gastroesophageal reflux disease after esophageal cancer surgery

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World Journal of Clinical Cases 2024年第13期12卷 2194-2200页

作者： Yu-Jing Zhang Shen-Ping Wu Department of Oncology Beijing Integrated Traditional Chinese and Western Medicine HospitalBeijing 100039China

BACKGROUND Gastroesophageal reflux disease(GERD)is a common complication of esophageal cancer surgery that can affect quality of life and increase the risk of esophageal stricture and anastomotic leakage.Wendan Decoction(WDD)is a traditional chinese herbal formula used to treat various gastrointestinal disorders,such as gastritis,functional dyspepsia,and irritable bowel syndrome.Mosapride,a prokinetic agent,functions as a selective 5-hydroxytryptamine 4 agonist,enhancing gastrointestinal motility.AIM To evaluate the therapeutic effects of WDD combined with mosapride on GERD after esophageal cancer surgery.METHODS Eighty patients with GERD were randomly divided into treatment(receiving WDD combined with mosapride)and control(receiving mosapride alone)groups.The treatment was conducted from January 2021 to January 2023.The primary outcome was improved GERD symptoms as measured using the reflux disease questionnaire(RDQ).The secondary outcomes were improved esophageal motility(measured using esophageal manometry),gastric emptying(measured using gastric scintigraphy),and quality of life[measured via the Short Form-36(SF-36)Health Survey].RESULTS The treatment group showed a notably reduced RDQ score and improved esophageal motility parameters,such as lower esophageal sphincter pressure,peristaltic amplitude,and peristaltic velocity compared to the control group.The treatment group showed significantly higher gastric emptying rates and SF-36 scores(in both physical and mental domains)compared to the control group.No serious adverse effects were observed in either group.CONCLUSION WDD combined with mosapride is an effective and safe therapy for GERD after esophageal cancer surgery.It can improve GERD symptoms,esophageal motility,gastric emptying,and the quality of life of patients.Further studies with larger sample sizes and longer follow-up periods are required to confirm these findings.

关键词： Gastroesophageal reflux disease Esophageal cancer surgery Wendan Decoction Mosapride Treatment effects Gastroesophageal reflux disease symptoms

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